tbuckley/cabot-search huggingface dataset:
Financial incentives for sustained smoking abstinence in pregnancy
Authors: Daniel Kotz, Jasper V Been
Journal: BMJ (2022)

Tobacco smoking during pregnancy is associated with an increased risk of stillbirth, low birth weight, preterm birth, sudden infant death syndrome, asthma, and obesity among offspring. 1Pregnancy is therefore an important window of opportunity to promote smoking cessation.Despite the risks, a substantial proportion of women worldwide still smoke during pregnancy. 2 Behavioural support and nicotine replacement therapy can support attempts to stop smoking during pregnancy. 3 4Financial incentives for pregnant smokers can increase smoking cessation rates further, 5 -8 and the linked paper by Tappin and colleagues (doi:10.
Myocarditis after BNT162b2 Vaccination in Israeli Adolescents
Authors: Guy Witberg, Ori Magen, Sara Hoss, Yeela Talmor-Barkan, Ilan Richter, Maya Wiessman, Yaron Aviv, Tzlil Grinberg, Arthur Shiyovich, Nili Schamroth-Pravda, Oren Auster, Noa Dagan, Einat Birk, Ran Balicer, Ran Kornowski
Journal: New England Journal of Medicine (2022)
Atrial Fibrillation — What Is It and How Is It Treated?
Authors: Elliott M. Antman, Jane A. Leopold, William H. Sauer, Paul C. Zei
Journal: New England Journal of Medicine (2022)

In this short documentary, renowned experts discuss how our understanding of the diagnosis and management of atrial fibrillation has changed, with a focus on new therapeutic options such as catheter ablation, all explained for patients and families.
Case 32-2022: A 76-Year-Old Man with Postoperative Cardiogenic Shock and Diffuse Rash
Authors: Akshay S. Desai, David M. Dudzinski, Matthew T. Stib, Steven T. Chen, Christopher Newton-Cheh, Kimberly G. Blumenthal, James R. Stone
Journal: New England Journal of Medicine (2022)

A 76-year-old man was evaluated for persistent postoperative cardiogenic shock and new diffuse rash after undergoing mitral-valve replacement. The patient received oxacillin. Management decisions were made.
COP27 Climate Change Conference—Urgent Action Needed for Africa and the World
Authors: Lukoye Atwoli, Gregory E. Erhabor, Aiah A. Gbakima, Abraham Haileamlak, Jean-Marie Kayembe Ntumba, James Kigera, Laurie Laybourn-Langton, Bob Mash, Joy Muhia, Fhumulani Mavis Mulaudzi, David Ofori-Adjei, Friday Okonofua, Arash Rashidian, Maha El-Adawy, Siaka Sidibé, Abdelmadjid Snouber, James Tumwine, Mohammad Sahar Yassien, Paul Yonga, Lilia Zakhama, Chris Zielinski
Journal: JAMA Network Open (2022)

Lukoye Atwoli; Gregory E. Erhabor; Aiah A. Gbakima; Abraham Haileamlak; Jean-Marie Kayembe Ntumba; James Kigera; Laurie Laybourn-Langton; Bob Mash; Joy Muhia; Fhumulani Mavis Mulaudzi; David Ofori-Adjei; Friday Okonofua; Arash Rashidian; Maha El-Adawy; Siaka Sidibé; Abdelmadjid Snouber; James Tumwine; Mohammad Sahar Yassien; Paul Yonga; Lilia Zakhama; Chris Zielinski
Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo
Authors: David Rosmarin, Thierry Passeron, Amit G. Pandya, Pearl Grimes, John E. Harris, Seemal R. Desai, Mark Lebwohl, Mireille Ruer-Mulard, Julien Seneschal, Albert Wolkerstorfer, Deanna Kornacki, Kang Sun, Kathleen Butler, Khaled Ezzedine
Journal: New England Journal of Medicine (2022)

Vitiligo is a chronic autoimmune disease that causes skin depigmentation. A cream formulation of ruxolitinib (an inhibitor of Janus kinase 1 and 2) resulted in repigmentation in a phase 2 trial involving adults with vitiligo.We conducted two phase 3, double-blind, vehicle-controlled trials (Topical Ruxolitinib Evaluation in Vitiligo Study 1 [TRuE-V1] and 2 [TRuE-V2]) in North America and Europe that involved patients 12 years of age or older who had nonsegmental vitiligo with depigmentation covering 10% or less of total body-surface area. Patients were randomly assigned in a 2:1 ratio to apply 1.5% ruxolitinib cream or vehicle control twice daily for 24 weeks to all vitiligo areas on the face and body, after which all patients could apply 1.5% ruxolitinib cream through week 52. The primary end point was a decrease (improvement) of at least 75% from baseline in the facial Vitiligo Area Scoring Index (F-VASI; range, 0 to 3, with higher scores indicating a greater area of facial depigmentation), or F-VASI75 response, at week 24. There were five key secondary end points, including improved responses on the Vitiligo Noticeability Scale.A total of 674 patients were enrolled, 330 in TRuE-V1 and 344 in TRuE-V2. In TRuE-V1, the percentage of patients with an F-VASI75 response at week 24 was 29.8% in the ruxolitinib-cream group and 7.4% in the vehicle group (relative risk, 4.0; 95% confidence interval [CI], 1.9 to 8.4; P<0.001). In TRuE-V2, the percentages were 30.9% and 11.4%, respectively (relative risk, 2.7; 95% CI, 1.5 to 4.9; P<0.001). The results for key secondary end points showed superiority of ruxolitinib cream over vehicle control. Among patients who applied ruxolitinib cream throughout 52 weeks, adverse events occurred in 54.8% in TRuE-V1 and 62.3% in TRuE-V2; the most common adverse events were application-site acne (6.3% and 6.6%, respectively), nasopharyngitis (5.4% and 6.1%), and application-site pruritus (5.4% and 5.3%).In two phase 3 trials, application of ruxolitinib cream resulted in greater repigmentation of vitiligo lesions than vehicle control through 52 weeks, but it was associated with acne and pruritus at the application site. Larger and longer trials are required to determine the effect and safety of ruxolitinib cream in patients with vitiligo. (Funded by Incyte; TRuE-V1 and TRuE-V2 ClinicalTrials.gov numbers, NCT04052425 and NCT04057573.).
New Hope for Patients with Vitiligo
Authors: Liv Eidsmo
Journal: New England Journal of Medicine (2022)

Vitiligo affects 0.5 to 2% of the population worldwide. This chronic autoimmune disease manifests as pale skin patches, caused by local death of pigment-producing melanocytes. The extent and perceived burden of disease vary, but lesions affecting the face and hands in persons with darker skin can be severely stigmatizing.1 The prognosis of vitiligo is difficult to predict because disease outcome is affected by both environmental and genetic factors. Effective treatments that induce long-term remission or cure are not yet available, and although topical use of the immunosuppressant drug tacrolimus or ultraviolet B (UVB) phototherapy2 can improve lesions affecting the face, . . .
Designing Interventions Addressing Structural Racism to Reduce Kidney Health Disparities: A Report from a National Institute of Diabetes and Digestive and Kidney Diseases Workshop
Authors: Deidra C. Crews, Rachel E. Patzer, Lilia Cervantes, Richard Knight, Tanjala S. Purnell, Neil R. Powe, Dawn P. Edwards, Keith C. Norris
Journal: Journal of the American Society of Nephrology (2022)

Structural racism embodies the many ways in which society fosters racial discrimination through "mutually reinforcing inequitable systems" that limit access to resources and opportunities that can promote health and well being among marginalized communities. To achieve health equity, and kidney health equity more specifically, structural racism must be eliminated. In February 2022, the National Institute of Diabetes and Digestive and Kidney Diseases convened the "Designing Interventions that Address Structural Racism to Reduce Kidney Health Disparities" workshop, which was aimed at describing the mechanisms through which structural racism contributes to health and health care disparities for people along the continuum of kidney disease and identifying actionable opportunities for interventional research focused on dismantling or addressing the effects of structural racism. Participants identified six domains as key targets for interventions and future research: (1) apply an antiracism lens, (2) promote structural interventions, (3) target multiple levels, (4) promote effective community and stakeholder engagement, (5) improve data collection, and (6) advance health equity through new health care models. There is an urgent need for research to develop, implement, and evaluate interventions that address the unjust systems, policies, and laws that generate and perpetuate inequities in kidney health.
Erratum: Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report Within the HARMONY Project
Journal: Journal of Clinical Oncology (2022)

In the Abstract, the third sentence of the Results section read, "A value was assigned to each risk feature according to their OS impact (ISS-III 1.5, ISS-II 1, del(17p) 1, high lactate dehydrogenase 1, and 1q1 0.5 points)."It should have read, "A value was assigned to each risk feature according to their OS impact (ISS-III 1.5, ISS-II 1, del(17p) 1, high lactate dehydrogenase 1, t(4;14) 1, and 1q1 0.5 points)."This has been corrected as of October 19, 2022.
Obstructive Sleep Apnea Symptoms Do Not Identify Patients at Risk of Chronic Kidney Disease
Authors: Andrew E. Beaudin, Jill K. Raneri, A.J. Marcus Hirsch Allen, Fréderic Series, R. John Kimoff, Robert P. Skomro, Najib T. Ayas, Diego R. Mazzotti, Brendan T. Keenan, Patrick J. Hanly
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Obstructive Sleep Apnea Symptoms Do Not Identify Patients at Risk of Chronic Kidney Disease." American Journal of Respiratory and Critical Care Medicine, 207(3), pp. 361–364
An 8-year pragmatic observation evaluation of the benefits of allogeneic HCT in older and medically infirm patients with AML
Authors: Mohamed L. Sorror, Ted A. Gooley, Barry E. Storer, Aaron T. Gerds, Mikkael A. Sekeres, Bruno C. Medeiros, Eunice S. Wang, Paul J. Shami, Kehinde Adekola, Selina Luger, Maria R. Baer, David A. Rizzieri, Tanya M. Wildes, Jamie Koprivnikar, Julie Smith, Mitchell Garrison, Kiarash Kojouri, Tammy A. Schuler, Wendy M. Leisenring, Lynn E. Onstad, Pamela S. Becker, Jeannine S. McCune, Stephanie J. Lee, Brenda M. Sandmaier, Frederick R. Appelbaum, Elihu H. Estey
Journal: Blood (2022)
Extended Follow-up of Microbiome Therapeutic SER-109 Through 24 Weeks for Recurrent <i>Clostridioides difficile</i> Infection in a Randomized Clinical Trial
Authors: Stuart H. Cohen, Thomas J. Louie, Matthew Sims, Elaine E. L. Wang, Asli Memisoglu, Barbara H. McGovern, Lisa von Moltke
Journal: JAMA (2022)

This study examines adverse events and durability of response of SER-109, an investigational microbiome therapeutic comprised of purified Firmicutes spores, compared with placebo for Clostridioides difficile infection.
Designing Interventions Addressing Structural Racism to Reduce Kidney Health Disparities: A Report from an NIDDK Workshop
Authors: Deidra Crews, Rachel Patzer, Lilia Cervantes, Richard Knight, Tanjala Purnell, Neil Powe, Dawn Edwards, Keith Norris
Journal: Journal of the American Society of Nephrology (2022)

Structural racism embodies the many ways in which society fosters racial discrimination through "mutually reinforcing inequitable systems" that limit access to resources and opportunities that can promote health and well-being among marginalized communities. To achieve health equity, and kidney health equity more specifically, structural racism must be eliminated. In February 2022, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) convened the "Designing Interventions that Address Structural Racism to Reduce Kidney Health Disparities" workshop which was aimed at describing the mechanisms through which structural racism contributes to health and healthcare disparities for people along the continuum of kidney disease; and identifying actionable opportunities for interventional research focused on dismantling or addressing the effects of structural racism. Participants identified six domains as key targets for interventions and future research: 1) apply an anti-racism lens, 2) promote structural interventions, 3) target multiple levels, 4) promote effective community and stakeholder engagement, 5) improve data collection, and 6) advance health equity through new healthcare models. There exists an urgent need for research to develop, implement and evaluate interventions that address the unjust systems, policies, and laws that generate and perpetuate inequities in kidney health.
Clinical Implications of a New DDX58 Pathogenic Variant That Causes Lupus Nephritis due to RIG-I Hyperactivation
Authors: Jiahui Peng, Yusha Wang, Xu Han, Changming Zhang, Xiang Chen, Ying Jin, Zhaohui Yang, Yu An, Jiahui Zhang, Zhengzhao Liu, Yinghua Chen, Erzhi Gao, Yangyang Zhang, Feng Xu, Chunxia Zheng, Qing Zhou, Zhihong Liu
Journal: Journal of the American Society of Nephrology (2022)

Significance Statement Lupus nephritis (LN) is the major cause of death among systemic lupus erythematosus patients, with heterogeneous phenotypes and different responses to therapy. Identifying genetic causes and finding potential therapeutic targets of LN is a major unmet clinical need. We identified a novel DDX58 pathogenic variant, R109C, that leads to RIG-I hyperactivation and type I IFN signaling upregulation by disrupting RIG-I autoinhibition, causing LN, which may respond to a JAK inhibitor. Genetic testing of families with multiple cases of LN that identifies this variant may lead to targeted therapy. Background Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus, with heterogeneous phenotypes and different responses to therapy. Identifying genetic causes of LN can facilitate more individual treatment strategies. Methods We performed whole-exome sequencing in a cohort of Chinese patients with LN and identified variants of a disease-causing gene. Extensive biochemical, immunologic, and functional analyses assessed the effect of the variant on type I IFN signaling. We further investigated the effectiveness of targeted therapy using single-cell RNA sequencing. Results We identified a novel DDX58 pathogenic variant, R109C, in five unrelated families with LN. The DDX58 R109C variant is a gain-of-function mutation, elevating type I IFN signaling due to reduced autoinhibition, which leads to RIG-I hyperactivation, increased RIG-I K63 ubiquitination, and MAVS aggregation. Transcriptome analysis revealed an increased IFN signature in patient monocytes. Initiation of JAK inhibitor therapy (baricitinib 2 mg/d) effectively suppressed the IFN signal in one patient. Conclusions A novel DDX58 R109C variant that can cause LN connects IFNopathy and LN, suggesting targeted therapy on the basis of pathogenicity.
Using human genetics to improve safety assessment of therapeutics
Authors: Keren J. Carss, Aimee M. Deaton, Alberto Del Rio-Espinola, Dorothée Diogo, Mark Fielden, Diptee A. Kulkarni, Jonathan Moggs, Peter Newham, Matthew R. Nelson, Frank D. Sistare, Lucas D. Ward, Jing Yuan
Journal: Nature Reviews Drug Discovery (2022)
Synaptogenic effect of <i>APP</i> -Swedish mutation in familial Alzheimer’s disease
Authors: Bo Zhou, Jacqueline G. Lu, Alberto Siddu, Marius Wernig, Thomas C. Südhof
Journal: Science Translational Medicine (2022)

Mutations in β-amyloid (Aβ) precursor protein ( APP ) cause familial Alzheimer’s disease (AD) probably by enhancing Aβ peptides production from APP. An antibody targeting Aβ (aducanumab) was approved as an AD treatment; however, some Aβ antibodies have been reported to accelerate, instead of ameliorating, cognitive decline in individuals with AD. Using conditional APP mutations in human neurons for perfect isogenic controls and translational relevance, we found that the APP -Swedish mutation in familial AD increased synapse numbers and synaptic transmission, whereas the APP deletion decreased synapse numbers and synaptic transmission. Inhibition of BACE1, the protease that initiates Aβ production from APP, lowered synapse numbers, suppressed synaptic transmission in wild-type neurons, and occluded the phenotype of APP -Swedish–mutant neurons. Modest elevations of Aβ, conversely, elevated synapse numbers and synaptic transmission. Thus, the familial AD-linked APP -Swedish mutation under physiologically relevant conditions increased synaptic connectivity in human neurons via a modestly enhanced production of Aβ. These data are consistent with the relative inefficacy of BACE1 and anti-Aβ treatments in AD and the chronic nature of AD pathogenesis, suggesting that AD pathogenesis is not simply caused by overproduction of toxic Aβ but rather by a long-term effect of elevated Aβ concentrations.
An ex vivo platform to guide drug combination treatment in relapsed/refractory lymphoma
Authors: Jasmine Goh, Sanjay De Mel, Michal M. Hoppe, Masturah Bte Mohd Abdul Rashid, Xi Yun Zhang, Patrick Jaynes, Esther Ka Yan Ng, Nur’Atiqa Diana Binti Rahmat, None Jayalakshmi, Clementine Xin Liu, Limei Poon, Esther Chan, Joanne Lee, Yen Lin Chee, Liang Piu Koh, Lip Kun Tan, Teck Guan Soh, Yi Ching Yuen, Hoi-Yin Loi, Siok-Bian Ng, Xueying Goh, Donovan Eu, Stanley Loh, Sheldon Ng, Daryl Tan, Daryl Ming Zhe Cheah, Wan Lu Pang, Dachuan Huang, Shin Yeu Ong, Chandramouli Nagarajan, Jason Yongsheng Chan, Jeslin Chian Hung Ha, Lay Poh Khoo, Nagavalli Somasundaram, Tiffany Tang, Choon Kiat Ong, Wee-Joo Chng, Soon Thye Lim, Edward K. Chow, Anand D. Jeyasekharan
Journal: Science Translational Medicine (2022)

Although combination therapy is the standard of care for relapsed/refractory non-Hodgkin's lymphoma (RR-NHL), combination treatment chosen for an individual patient is empirical, and response rates remain poor in individuals with chemotherapy-resistant disease. Here, we evaluate an experimental-analytic method, quadratic phenotypic optimization platform (QPOP), for prediction of patient-specific drug combination efficacy from a limited quantity of biopsied tumor samples. In this prospective study, we enrolled 71 patients with RR-NHL (39 B cell NHL and 32 NK/T cell NHL) with a median of two prior lines of treatment, at two academic hospitals in Singapore from November 2017 to August 2021. Fresh biopsies underwent ex vivo testing using a panel of 12 drugs with known efficacy against NHL to identify effective single and combination treatments. Individualized QPOP reports were generated for 67 of 75 patient samples, with a median turnaround time of 6 days from sample collection to report generation. Doublet drug combinations containing copanlisib or romidepsin were most effective against B cell NHL and NK/T cell NHL samples, respectively. Off-label QPOP-guided therapy offered at physician discretion in the absence of standard options (n = 17) resulted in five complete responses. Among patients with more than two prior lines of therapy, the rates of progressive disease were lower with QPOP-guided treatments than with conventional chemotherapy. Overall, this study shows that the identification of patient-specific drug combinations through ex vivo analysis was achievable for RR-NHL in a clinically applicable time frame. These data provide the basis for a prospective clinical trial evaluating ex vivo-guided combination therapy in RR-NHL.
Lean body mass and the cardiovascular system constitute a female-specific relationship
Authors: Candela Diaz-Canestro, Brandon Pentz, Arshia Sehgal, Ranyao Yang, Aimin Xu, David Montero
Journal: Science Translational Medicine (2022)

Recent evidence points toward a link between lean body mass (LBM) and cardiovascular capacity in women. This study aimed at determining the sex-specific relationship of LBM with central and peripheral circulatory variables in healthy women and men ( n =70) matched by age (60±12 years versus 58±15 years), physical activity, and cardiovascular risk factors. Regional (legs, arms, and trunk) and whole-body (total) body composition were assessed via dual-energy x-ray absorptiometry. Cardiac structure, function, and central/peripheral hemodynamics were measured via transthoracic echocardiography and the volume-clamp method at rest and peak incremental exercise. Regression analyses determined sex-specific relationships between LBM and cardiovascular variables. Regional and total LBM were lower in women than men ( P &lt;0.001), with little overlap between sexes. Leg and arm LBM positively associated with left ventricular (LV) internal resting dimensions in women ( r ≥0.53, P ≤0.002) but not men ( P ≥0.156). Leg, arm, and total LBM only associated with LV relaxation in women ( r ≥0.43, P ≤0.013). All LBM variables strongly associated with LV volumes at peak exercise in women ( r ≥0.54, P ≤0.001) but not men and negatively associated with total peripheral resistance at peak exercise in women ( r ≥0.43, P ≤0.023). Adjustment by adiposity-related or cardiovascular risk factors did not alter results. In conclusion, leg and arm LBM independently associate with internal cardiac dimensions, ventricular relaxation, and systemic vascular resistance in a sex-specific manner, with these relationships exclusively present in women.
The anticancer human mTOR inhibitor sapanisertib potently inhibits multiple <i>Plasmodium</i> kinases and life cycle stages
Authors: Lauren B. Arendse, James M. Murithi, Tarrick Qahash, Charisse Flerida A. Pasaje, Luiz C. Godoy, Sumanta Dey, Liezl Gibhard, Sonja Ghidelli-Disse, Gerard Drewes, Marcus Bantscheff, Maria J. Lafuente-Monasterio, Stephen Fienberg, Lynn Wambua, Samuel Gachuhi, Dina Coertzen, Mariëtte van der Watt, Janette Reader, Ayesha S. Aswat, Erica Erlank, Nelius Venter, Nimisha Mittal, Madeline R. Luth, Sabine Ottilie, Elizabeth A. Winzeler, Lizette L. Koekemoer, Lyn-Marie Birkholtz, Jacquin C. Niles, Manuel Llinás, David A. Fidock, Kelly Chibale
Journal: Science Translational Medicine (2022)

Compounds acting on multiple targets are critical to combating antimalarial drug resistance. Here, we report that the human “mammalian target of rapamycin” (mTOR) inhibitor sapanisertib has potent prophylactic liver stage activity, in vitro and in vivo asexual blood stage (ABS) activity, and transmission-blocking activity against the protozoan parasite Plasmodium spp. Chemoproteomics studies revealed multiple potential Plasmodium kinase targets, and potent inhibition of Plasmodium phosphatidylinositol 4-kinase type III beta (PI4Kβ) and cyclic guanosine monophosphate–dependent protein kinase (PKG) was confirmed in vitro. Conditional knockdown of PI4Kβ in ABS cultures modulated parasite sensitivity to sapanisertib, and laboratory-generated P. falciparum sapanisertib resistance was mediated by mutations in PI4Kβ. Parasite metabolomic perturbation profiles associated with sapanisertib and other known PI4Kβ and/or PKG inhibitors revealed similarities and differences between chemotypes, potentially caused by sapanisertib targeting multiple parasite kinases. The multistage activity of sapanisertib and its in vivo antimalarial efficacy, coupled with potent inhibition of at least two promising drug targets, provides an opportunity to reposition this pyrazolopyrimidine for malaria.
Change the Framework for Pulse Oximeter Regulation to Ensure Clinicians Can Give Patients the Oxygen They Need
Authors: Michael W. Sjoding, Theodore J. Iwashyna, Thomas S. Valley
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Change the Framework for Pulse Oximeter Regulation to Ensure Clinicians Can Give Patients the Oxygen They Need." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –